The Annals of Statistics

Markov chains for Monte Carlo tests of genetic equilibrium in multidimensional contingency tables

Kenneth Lange and Laura C. Lazzeroni

Full-text: Open access

Abstract

Hardy-Weinberg equilibrium and linkage equilibrium are fundamental concepts in population genetics. In practice, testing linkage equilibrium in haplotype data is equivalent to testing independence in a large, sparse, multidimensional contingency table. Testing Hardy-Weinberg and linkage equilibrium simultaneously on multilocus genotype data introduces the additional complications of missing information and symmetry constraints on marginal probabilities. To avoid unreliable large-sample approximations for sparse contingency tables, one can use exact tests like Fisher's classical test that condition on observed marginal totals. Unfortunately, computing p-values for exact tests is often infeasible because of the large number of tables consistent with the marginal totals of an observed table. We develop here Markov chains for sampling from the appropriate conditional distributions for testing genetic equilibrium. These chains compare favorably with a parallel, independent-sampling method that we present. For n haplotype observations on J loci, the Markov chains converge to their stationary distributions in $[(J - 1)n 1n n]/2 + O(n)$ steps and can be an efficient tool for estimating p-values. Our theoretical treatment of these results involves strong stationary stopping times, order statistics, large deviations and the embedding of Poisson processes. We include some general results on the application of strong stationary times to bounding the precision and bias of sample average estimators.

Article information

Source
Ann. Statist. Volume 25, Number 1 (1997), 138-168.

Dates
First available in Project Euclid: 10 October 2002

Permanent link to this document
http://projecteuclid.org/euclid.aos/1034276624

Digital Object Identifier
doi:10.1214/aos/1034276624

Mathematical Reviews number (MathSciNet)
MR1429920

Zentralblatt MATH identifier
0871.62094

Subjects
Primary: 62P10: Applications to biology and medical sciences 65C05: Monte Carlo methods

Keywords
Exact inference strong stationary stopping time large deviations Hardy-Weinberg linkage equilibrium independent sampling random transpositions

Citation

Lazzeroni, Laura C.; Lange, Kenneth. Markov chains for Monte Carlo tests of genetic equilibrium in multidimensional contingency tables. Ann. Statist. 25 (1997), no. 1, 138--168. doi:10.1214/aos/1034276624. http://projecteuclid.org/euclid.aos/1034276624.


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  • STANFORD, CALIFORNIA 94305 ANN ARBOR, MICHIGAN 48109 E-MAIL: laura@play fair.stanford.edu E-MAIL: klange@sph.umich.edu